Unravelling the Pathogenesis of Celia’s Encephalopathy (PELD): The Role of Seipin in Neurodegeneration, Lipodystrophy, and other Tissue Damage in a Humanized Murine Model

Abstract

Lipodystrophies are rare disorders, with Celia’s encephalopathy, identified by our research group in 2013, being exceptionally rare with only 33 cases to date. Over the years, our research group has unravelled key pathogenic mechanisms of this disease. However, its rarity, severity, and predominant brain involvement pose significant challenges for human studies. Therefore, in this study, we developed a knock-in mouse model expressing the aberrant human BSCL2 transcript, alongside a Bscl2 knock out model, to compare the effects of BSCL2 deficiency and overexpression. These models replicate aspects of Celia’s encephalopathy and congenital generalized lipodystrophy, offering valuable preclinical tools for studying these conditions and exploring potential therapies.